The majority of immunoglobulin in tears is of the immunoglobulin A (IgA) isotype, which is produced mainly by plasma cells of the lacrimal gland. The mechanism responsible for the lodging of IgA plasma cells in this gland is unknown and probably not dependent on direct glandular encounter with antigen. Previous experiments have demonstrated that an epithelial cell of the lacrimal gland can influence isotype committed B lymphocytes to differentiate into IgA plasma cells. The proposed investigations will examine lacrimal epithelial cells in order to define the mechanism leading to the selective lodging of IgA committed lymphoid cells within glandular tissue. For epithelial cells to affect lymphoid cells in this manner, lymphoid cells must traverse extravascular regions of the microenvironment of the lacrimal gland. Therefore a second portion of these studies will examine the migration of lymphocytes through the normal lacrimal gland. Although IgA is the predominant isotype of immunoglobulin in tears, a specific function for this immunoglobulin has not been demonstrated in disease immunopathogenesis. Immunoglobulin A has been shown to interfere with bacterial adherence to epithelial cells along other mucosal surfaces, and by analogy, could function in a similar manner in preventing this initial step in cell infection. These studies will attempt to explain the predominance of IgA-producing cells along mucosal surfaces, with the long term goal of altering the numbers of such antibody-producing cells, depending on their role in disease immunopathogenesis. Aditionally, a role for IgA antibody in preventing HSV1 attachment to ocular surface cells will be examined in order to better understand the mechanisms involved in this most important infectious disease of the ocular surface structures.